Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice

A. Ota, Y. S. Kaneko, K. Mori, Akira Nakashima, I. Nagatsu, T. Nagatsu

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.

Original languageEnglish
Pages (from-to)131-136
Number of pages6
JournalStress
Volume10
Issue number2
DOIs
Publication statusPublished - 01-06-2007

Fingerprint

GTP Cyclohydrolase
Locus Coeruleus
Lipopolysaccharides
Norepinephrine
Methoxyhydroxyphenylglycol
Endotoxemia
Tyrosine 3-Monooxygenase
Septic Shock
Gram-Negative Bacteria
Neuroblastoma
Endotoxins
Cytokines
Gene Expression
Cell Line
Messenger RNA
Membranes
sapropterin
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Neuropsychology and Physiological Psychology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Behavioral Neuroscience

Cite this

@article{ecf64a50701246f0b412d9bea18e7465,
title = "Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice",
abstract = "Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.",
author = "A. Ota and Kaneko, {Y. S.} and K. Mori and Akira Nakashima and I. Nagatsu and T. Nagatsu",
year = "2007",
month = "6",
day = "1",
doi = "10.1080/10253890701350511",
language = "English",
volume = "10",
pages = "131--136",
journal = "Stress",
issn = "1025-3890",
publisher = "Informa Healthcare",
number = "2",

}

Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice. / Ota, A.; Kaneko, Y. S.; Mori, K.; Nakashima, Akira; Nagatsu, I.; Nagatsu, T.

In: Stress, Vol. 10, No. 2, 01.06.2007, p. 131-136.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice

AU - Ota, A.

AU - Kaneko, Y. S.

AU - Mori, K.

AU - Nakashima, Akira

AU - Nagatsu, I.

AU - Nagatsu, T.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.

AB - Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.

UR - http://www.scopus.com/inward/record.url?scp=34249102925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249102925&partnerID=8YFLogxK

U2 - 10.1080/10253890701350511

DO - 10.1080/10253890701350511

M3 - Review article

C2 - 17514581

AN - SCOPUS:34249102925

VL - 10

SP - 131

EP - 136

JO - Stress

JF - Stress

SN - 1025-3890

IS - 2

ER -